The present invention relates to poly-ion complex comprising chitin or N-acylchitosan derivative having carboxylic acid group and polyelectrolyte (hereinafter abbreviated as PC). More in detail, the present invention relates to poly-ion complex obtained by subjecting carboxymethyl N-acylchitosan or de-N-acylated carboxymethyl N-acylchitosan, which is soluble in an aqueous solvent and is an anionic or amphoteric high polymeric electrolyte or its salt to a reaction with anionic or cationic polymer in an aqueous solvent, and a process for preparing the poly-ion complex, and further relates to poly-ion complex obtained by subjecting carboxymethylchitin or deacetylated carboxymethylchitin, which is soluble in an aqueous solvent and is an anionic or amphoteric high polymeric electrolyte or its salt to a reaction with anionic or cationic polymer in an aqueous solvent; and a process for preparing the poly-ion complex.
The PC is a complex compound obtained by subjecting a positive-charged polyelectrolyte to a reaction with a negative-charged polyelectrolyte in a solvent; obtained by subjecting a positive-charged polyelectrolyte to a reaction with an amphoteric polyelectrolyte; or obtained by subjecting a negative-charged polyelectrolyte to a reaction with an amphoteric polyelectrolyte.
The reaction is very interesting as a model of reactions in living bodies such as those represented by a mutual reaction between a polysaccharide and a protein. Recently, the materials obtained by utilizing the above-mentioned reaction for forming PC are attracting the attention as a functional material for medical treatments or for living bodies, for instance, a dialysis membrane and filter material for use in ultrafiltration.
In cases where the PC-material is used as a material for living body, it is indispensable that the component of PC or PC itself is compatible with, non-toxic to and stable within or without the living body.
In these points, chitin or N-acylchitosan is chemically stable also within the living body and safe to the living body, however, since chitin is highly crystalline in nature and its bonding with aminoacetyl group is strong, no solvent is available for dissolving, dispersing or swelling chitin so favorably as is in the case of cellulose.
For instance, dichloroacetic acid, sulfuric acid and formic acid are mentioned as a solvent for chitin or N-acylchitosan. However, these solvents cause the reduction of molecular weight or the degradation of chitin or N-acylchitosan, and have several problems of handling such as treatment of waste liquor. Accordingly, in order to convert chitin into a soluble derivative in safer solvents, several trials have been carried out such as alkylation or acetylation of chitin.
For instance, the deacetylated chitin, i.e., chitosan and its derivatives have been proposed.
As a PC using chitin as its starting material, the PC of chitosan and a sulfonated polyvinyl alcohol (Japanese Patent Application Laid Open No. 8879/75) and the PC of chitosan and sulfonated cellulose (Japanese Patent Application Laid Open No. 123,179/75) have been proposed.
The inventors of the present invention have found in the studies for utilizing and developing chitin or N-acylchitosan derivative which is the carboxymethylchitin, the deacetylated carboxymethylchitin, the carboxymethyl N-acylchitosan, the de-N-acylated carboxymethyl N-acylchitosan or its salt. The carboxymethylchitin, the carboxymethyl N-acylchitosan or its salt is soluble in an aqueous alkaline solution. The deacetylated carboxymethylchitan, the de-N-acylated carboxymethyl N-acylchitosan or its salt is soluble in an aqueous acidic or alkaline solution and also in an aqueous solution of a neutral salt at a moderately high concentration. Moreover, the above-mentioned deacetylated derivative is an amphoteric polyelectrolyte having carboxyl and amino groups. It is an object of the present invention to provide a poly-ion complex comprising: chitin or N-acylchitosan derivative having carboxymethyl; and a polyelectrolyte. The chitin derivative is carboxymethylchitin, an amphoteric deacetylated carboxymethylchitin or its salt. The N-acylchitosan derivative is carboxymethyl N-acylchitosan, de-N-acylated carboxymethyl N-acylchitosan or its salt. The PC according to the present invention is extremely well soluble in aqueous solvents, and has favorably high processability.
For instance, carboxymethylchitin and the deacetylated derivative of carboxymethylchitin for use in the present invention are obtainable, for instance, by the following procedures:
Chitin represented by the following general formula (I) obtained by separation from crusts of crustaceans such as crabs and lobsters and purification in a conventional method is brought into reaction with monochloroacetic acid to be carboxymethylated to carboxymethylchitin or its salt represented by the general formula (II): ##STR1## wherein M represents a hydrogen atom, alkali metal, alkaline earth metal or an ammonium group; m.sub.1, m.sub.3, n, n.sub.1 and n.sub.2 represent any positive integer; m.sub.2 and m.sub.4 represent zero or any positive integer.
In carboxymethyl N-acylchitosan or its salt of the present invention, the carboxymethylation degree per pyranose unit, which is a structural unit, is 0.1 to 1.0, preferably 0.3 to 1.0.
In the next place, the above-mentioned carboxymethyl N-acetylchitosan or its salt is heated in an aqueous alkaline solution, for instance, sodium hydroxide or potassium hydroxide to cause deacylation to obtain the amphoteric polyelectrolyte in an aqueous solvent, i.e., the de-N-acylated carboxymethyl N-acylchitosan or its salt for use in the present invention. The de-N-acylation degree of the deacylated substance is 0.1 to 1.0, preferably 0.3 to 1.0 per pyranose unit.
In carboxymethylchitin or its salt of the present invention, the carboxymethylation degree per pyranose unit, which is a structural unit, is 0.1 to 1.0, preferably 0.3 to 1.0.
In the next place, the above-mentioned carboxymethylchitin or its salt is heated in an aqueous alkaline solution, for instance, sodium hydroxide or potassium hydroxide to cause deacetylation to obtain the amphoteric polyelectrolyte in an aqueous solvent, i.e., the deacetylated carboxymethylchitin or its salt for use in the present invention. The deacetylation degree of the deacetylated substance is 0.1 to 1.0, preferably 0.3 to 1.0 per pyranose unit. (The example of producing the deacetylated product of carboxymethylchitin is described in Japanese Patent Application No. 161,391).
The typical composition units of carboxymethylchitin, deacetylated carboxymethylchitin, carboxymethyl N-acylchitosan and de-N-acylated carboxymethyl N-acylchitosan of the present invention are exemplified as follows by using simplified structural formulae: ##STR2## wherein R represents alkyl having 1 to 12 carbon atoms.
It is difficult to indicate the structure of PC of the present invention clearly by a chemical formula, however, it is presumed that the PC has a net-work of three dimensional structure comprising mainly electrostatic bonding between --NH.sub.3.sup..sym. of the de-N-acylated carboxymethyl N-acylchitosan and an anionic group of a polyelectrolyte or between --COO.sup..crclbar. of the de-N-acylated carboxymethyl N-acylchitosan and a cationic group of a polyelectrolyte.
The polyelectrolytes for use in the present invention are divided into the following four groups:
(1) A group of aqueous solution-soluble chitosan derivatives, for instance, chitosan, glycol-chitosan, glycelide-chitosan, N-methylglycol-chitosan, etc., those having amino group(s),
(2) A group of sulfated chitin derivatives or chitosan derivatives, both being aqueous solution-soluble, for instance, anionic ones such as O-sulfated chitin, N-sulfated chitosan or N-sulfated, glycol-chitosan, or O- and N-sulfated chitosan and glycol-chitosan, for instance, chitosan sulfuric acid ester, chitin sulfuric acid ester and glycol-chitosan sulfuric acid ester.
(3) A group consisting of dextran sulfate, hepalin and chondroitin sulfuric acid (chondroitin sulfate).
(4) A group of anionic- or cationic aqueous solution-soluble polymers. As an anionic polymer, for instance, polystyrenesulfonate, polyethylenesulfonate, partially sulfated polyvinyl alcohol, polyacrylate, polymethacrylate and poly-L-glutamate are used; and as a cationic polymer, for instance, poly-L-lysine, polyethyleneimine, polyvinylpyridine, polyvinylbenzyltrimethylammonium salt and polydiallyldimethylammonium salt are used.
The inonic polyelectrolytes used in the present invention are soluble in an aqueous solvent and accordingly, the PC of the present invention is easily produced without using any organic solvent. That is, the PC according to the present invention may be obtained by dissolving the carboxymethyl N-acylchitosan, the de-N-acylated carboxymethyl N-acylchitosan or its salt in an aqueous solvent and adding to the solution a solution of cationic- or anionic polyelectrolyte under stirring and then separating and washing the thus formed PC with water.
The aqueous solvent for use in the above-mentioned reaction is an aqueous acidic- or alkaline solution. The concentration of the solute (acid or alkali) can be selected freely, however, in consideration of the viscosity of the solution, usually is 0.1 to 5% by weight. Care should be taken, because of the formation of non-uniform PC or of gel-like PC, not to make the viscosity too high. The reaction temperature for the PC is preferably below 100.degree. C., because the solvent is aqueous, and more preferably at the vicinity of room temperature.
The confirmation of the formation of PC is possibly carried out by elementary analysis, infrared spectroscopy and solubility test. The limiting viscosity (.eta..sub.sp /c) at a temperature of 20.degree. C. (determined by the Ubbelohde viscometer) of the PC of the present invention is 0.1 to 20.
The PC obtained according to the present invention is soluble in an aqueous solution of pH at which the partner of the carboxymethyl N-acylchitosan, the de-N-acylated carboxymethyl N-acylchitosan or its salt is soluble and also is soluble in an aqueous solution of a neutral salt. In this point, the PC of the present invention is extremely high in processability.
For instance, it is soluble into the aqueous solution of sodium chloride, potassium chloride, calcium chloride, magnesium chloride, ammonium chloride, etc. or sodium, potassium, magnesium or ammonium salt of an organic acid such as acetic-, adipic-, propionic-, mandelic-, salicylic- and succinic acid.
Accordingly, after dissolving the PC of the present invention into one of the above-mentioned solution and shaping it into film-like of fiber-like bodies, insolbilization is easily carried out by desalting treatment.
The electrodeposition method of G.B. Pat. No. 1,153,551 may be used for preparation of the shaped material from the above-mentioned solution. In this case, deacetylated carboxymethylchitin or de-N-acylated carboxymethyl N-acylchitosan is very utilizable owing to an amphoteric polyelectrolyte. In either condition of acidic or basic aqueous solution, the shaped material is obtained by electrophoresis and then electrodeposit of the amphoteric polyelectrolyte with other constituent of anionic or cationic polyelectrolyte.
This insolubilization is made further complete by thermal treatment, treatment by ultraviolet rays and treatment by a cross-linking agent.
The shaped bodies of the PC of the present invention is excellent in chemical proofness and thermal resistance and based on a chitin or N-acylchitosan derivative, and so it is stable within the living bodies. And because of having ionic groups, it is utilizable as a material for microcapsule, for edible casing or for membrane for use in dialysis and ultrafiltration in artificial organs and for surgical operation, for membrane as a separator in accumulator, for membrane of fuel cells, a material of plastics regulating humidity and a coating material for electroconductivity or for preventing electric charging.